From 'hit' to candidate: Inside Sanofi's massive compound sharing agreement with AZ
Last November, Sanofi and AstraZeneca struck a major chemical compound sharing agreement, agreeing to exchange over 210,000 compounds from their respective collections. The deal aims to increase the chemical diversity of each company’s drug "library," and hopefully boost the number of leads for future drugs.
BioPharma Dive recently spoke with Dr. Gary Nabel, the chief scientific officer at Sanofi, on the value of this kind of collaboration and how the screening process would get off the ground. In our conversation, Nabel also touched on how Sanofi hopes to build off its experience working on its recently licensed dengue vaccine in its hunt for a Zika virus vaccine.
While Sanofi hasn’t initiated any screening on the exchanged compounds as of yet, the agreement with AstraZeneca is a bet on future discoveries with little immediate cost to either firm.
Boosting throughput to increase future leads
Nabel held up the collaboration as an example of the kind of business innovation that can help boost advancements in the underlying science. At the same time, he cautioned the process of taking a compound from an initial “hit” to a drug candidate can be long and complicated.
The compounds exchanged were chosen to fill respective gaps in each company’s existing library. Each company will be able to conduct high throughput screening (HTS) upon request. With HTS, the aim is to screen for compounds which are active against a specific biological target or pathway.
Once a “hit” is identified, the molecule will be analyzed for toxicities or other properties which adversely affect organ function. The process will attempt to identify molecules with minimal side effects before proceeding to further testing. Over time, “hits” will be winnowed down into leads and, eventually, drug candidates.
“The real downfall of most small molecules is not efficacy, it is toxicity,” explained Nabel. “Navigating that path is really a challenge. It is like the old mythical tale of Scylla and Charybdis. You have very small channels to navigate through.”
This is where the compound exchange comes in. By increasing the chemical diversity of their libraries, both Sanofi and AstraZeneca have a larger pool to draw from to put through this lengthy process.
A brave new world
The exchange gives Sanofi and AstraZeneca an opportunity to explore new compounds with their respective screening techniques, potentially revealing value the other didn’t identify. Nabel sees more big companies taking this approach, and collaborating with each other and with smaller biotechs.
“We are in a brave new world of small molecule development. Library sharing is one way of doing it,” said Nabel. “It offers the possibility of identifying new medicines that can really make a difference for some of the challenging diseases.”
Pathway to Zika?
In early February, the company announced it had launched a Zika vaccine R&D project as concerns over the disease’s spread mounted. In some ways, Nabel saw similarities between the compound exchange and the process of leveraging Sanofi’s dengue vaccine to explore options against Zika.
“By having recently licensed an effective vaccine against dengue, it really gives us what I would call a platform on which to build an effort against Zika,” Nabel said.
Back in December 2015, Sanofi won approval for its Dengue vaccine—the world’s first—in Mexico, the Philippines, and Brazil. The vaccine, known as dengvaxia, notched another win when El Salvador approved the vaccine early in the first quarter of this year. Further regulatory decisions are pending in 16 other countries.
For Dengvaxia, Sanofi modified the yellow fever virus by removing the surface part of the virus and replacing it with the dengue virus’ surface molecule. This attenuated version of yellow fever exposes patients to the parts of dengue which give immunity.
Nabel explained that Sanofi hopes to do the same thing with Zika, and replace the yellow fever surface molecule with Zika. “This is why we think it is worth trying this platform against Zika because we can do an exactly analogous thing.” Dengue and Zika are both a type of flavivirus, and are transmitted by the same mosquito.
But even with Sanofi’s development experience, a Zika vaccine is not around the corner just yet. “For this, if it were anything less than three years, it would be phenomenal.”
Sanofi also has competition. A number of major pharmas have announced efforts to identify a Zika vaccine, including Japan's Takeda, Pfizer, and Merck.
India-based Bharat Biotech may be the farthest along, however. It recently revealed it has been working on two vaccine candidates for more than a year. One, an inactivated vaccine, will begin animal testing soon.
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